The primary objectives of this proposal are to obtain an understanding of cellular interactions during axonal degeneration and regeneration and to employ this understanding in further analysis of the cross-regenerate model. The specific aims are to: a.) describe degeneration in identified axons following axotomy with emphasis on interactions between axons and glia during die-back of the proximal stump and degeneration of the distal stump; b.) observe the growth of regenerating fibers from identified axons in order to determine their number, branching pattern and the specificity with which they re-innervate their target; c.) discover the role of trophic interactions between muscle and axons of two functional types (excitatory and inhibitory) in maintaining both muscle morphology and the topography of terminal axon branches; d.) determine whether normal pattern of matching between transmitter release properties of axon terminals and contraction characteristics of muscle fibers is re-established in regenerates; e.) analyze reflex responsiveness of motor neurons following axotomy; f.) determine if reflexes can be predictably established in cross-regenerate organisms and to study the interaction of these reflexes with central pattern generators. A simple motor system will be employed in pursuit of these aims. The system is comprised of a single muscle and the five identifiable axons, two excitors and three inhibitors, which innervate it. The two excitors reach the muscle via a different ganglionic root than the inhibitors, thus allowing for selective ablation of one or the other functional type of innervation. The cross-regenerate (an organism which has the proximal end of one leg nerve crossed to the contralateral side, and allowed to regenerate) is an experimental model for examining the specificity of regeneration and for studying the influence of identified sensory organs in one leg on the rhythmic motor patterns produced in the contralateral, unrestrained limb. Preliminary results lead to the suggestion that the glial response during axonal degeneration and die-back, in this system, is remarkably similar to that observed in vertebrate toxic neuropathies. Therefore, this system may present a model system for identifying general gactors responsible for degenerative glial invasion of the axolemma.